Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Pediatric Mental Health Emergency Department Visits From 2017 To 2022: A Multicenter Study, Jennifer A Hoffmann, Camille P Carter, Cody S Olsen, David Ashby, Kamali L Bouvay, Susan J Duffy, James M Chamberlain, Sofia S Chaudhary, Nicolaus W Glomb, Jacqueline Grupp-Phelan, Maya Haasz, Erin P O'Donnell, Mohsen Saidinejad, Bashar S Shihabuddin, Leah Tzimenatos, Neil G Uspal, Joseph J Zorc, Lawrence J Cook, Elizabeth R Alpern

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic adversely affected children's mental health (MH) and changed patterns of MH emergency department (ED) utilization. Our objective was to assess how pediatric MH ED visits during the COVID-19 pandemic differed from expected prepandemic trends.

Methods: We retrospectively studied MH ED visits by children 5 to < 18 years old at nine U.S. hospitals participating in the Pediatric Emergency Care Applied Research Network Registry from 2017 to 2022. We described visit length by time period: prepandemic (January 2017-February 2020), early pandemic (March 2020-December 2020), midpandemic (2021), and late pandemic (2022). We estimated expected visit rates from prepandemic data using multivariable Poisson regression models. We calculated rate ratios (RRs) of observed to expected visits per 30 days during each pandemic time period, overall and by sociodemographic and clinical characteristics.

Results: We identified 175,979 pediatric MH ED visits. Visit length exceeded 12 h for 7.3% prepandemic, 8.4% early pandemic, 15.0% midpandemic, and 19.2% late pandemic visits. During the early pandemic, observed visits per 30 days decreased relative to expected rates (RR 0.80, 95% confidence interval [CI] 0.78-0.84), were similar to expected …

Psmd11 Loss-Of-Function Variants Correlate With A Neurobehavioral Phenotype, Obesity, And Increased Interferon Response, Wallid Deb, Cory Rosenfelt, Virginie Vignard, Jonas Johannes Papendorf, Sophie Möller, Martin Wendlandt, Maja Studencka-Turski, Benjamin Cogné, Thomas Besnard, Léa Ruffier, Bérénice Toutain, Léa Poirier, Silvestre Cuinat, Amy Kritzer, Amy Crunk, Janette Dimonda, Jaime Vengoechea, Sandra Mercier, Lotte Kleinendorst, Mieke M Van Haelst, Linda Zuurbier, Telma Sulem, Hildigunnur Katrínardóttir, Rún Friðriksdóttir, Patrick Sulem, Kari Stefansson, Berglind Jonsdottir, Shimriet Zeidler, Margje Sinnema, Alexander P A Stegmann, Natali Naveh, Cara M Skraban, Christopher Gray, Jill R Murrell, Sedat Isikay, Davut Pehlivan, Daniel G Calame, Jennifer E Posey, Mathilde Nizon, Kirsty Mcwalter, James R Lupski, Bertrand Isidor, François V Bolduc, Stéphane Bézieau, Elke Krüger, Sébastien Küry, Frédéric Ebstein

Faculty, Staff and Students Publications

Primary proteasomopathies have recently emerged as a new class of rare early-onset neurodevelopmental disorders (NDDs) caused by pathogenic variants in the PSMB1, PSMC1, PSMC3, or PSMD12 proteasome genes. Proteasomes are large multi-subunit protein complexes that maintain cellular protein homeostasis by clearing ubiquitin-tagged damaged, misfolded, or unnecessary proteins. In this study, we have identified PSMD11 as an additional proteasome gene in which pathogenic variation is associated with an NDD-causing proteasomopathy. PSMD11 loss-of-function variants caused early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity in 10 unrelated children. Our findings demonstrate that the cognitive impairment observed in these individuals could be …

Developmental Milestones And Daily Living Skills In Individuals With Angelman Syndrome, Anjali Sadhwani, Sonya Powers, Anne Wheeler, Hillary Miller, Sarah Nelson Potter, Sarika U Peters, Carlos A Bacino, Steven A Skinner, Logan K Wink, Craig A Erickson, Lynne M Bird, Wen-Hann Tan

Faculty, Staff and Students Publications

BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants.

METHODS: Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living …

Exome Sequencing Implicates Ancestry-Related Mendelian Variation At Syne1 In Childhood-Onset Essential Hypertension, Ian Copeland, Edmond Wonkam-Tingang, Monesha Gupta-Malhotra, S Shahrukh Hashmi, Yixing Han, Aarti Jajoo, Nancy J Hall, Paula P Hernandez, Natasha Lie, Dan Liu, Jun Xu, Jill Rosenfeld, Aparna Haldipur, Zelene Desire, Zeynep H Coban-Akdemir, Daryl A Scott, Qing Li, Hsiao-Tuan Chao, Ana M Zaske, James R Lupski, Dianna M Milewicz, Sanjay Shete, Jennifer E Posey, Neil A Hanchard

Faculty, Staff and Student Publications

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date. Here, we identify recessive segregation of rare and putatively damaging missense variation in the spectrin domain of spectrin repeat containing nuclear envelope …

Gain-Of-Function And Loss-Of-Function Variants In Gria3 Lead To Distinct Neurodevelopmental Phenotypes, Berardo Rinaldi, Allan Bayat, Linda G Zachariassen, Jia-Hui Sun, Yu-Han Ge, Dan Zhao, Kristine Bonde, Laura H Madsen, Ilham Abdimunim Ali Awad, Duygu Bagiran, Amal Sbeih, Syeda Maidah Shah, Shaymaa El-Sayed, Signe M Lyngby, Miriam G Pedersen, Charlotte Stenum-Berg, Louise Claudia Walker, Ilona Krey, Andrée Delahaye-Duriez, Lisa T Emrick, Krystal Sully, Chaya N Murali, Lindsay C Burrage, Julie Ana Plaud Gonzalez, Mered Parnes, Jennifer Friedman, Bertrand Isidor, Jérémie Lefranc, Sylvia Redon, Delphine Heron, Cyril Mignot, Boris Keren, Mélanie Fradin, Christele Dubourg, Sandra Mercier, Thomas Besnard, Benjamin Cogne, Wallid Deb, Clotilde Rivier, Donatella Milani, Maria Francesca Bedeschi, Claudia Di Napoli, Federico Grilli, Paola Marchisio, Suzanna Koudijs, Danielle Veenma, Emanuela Argilli, Sally Ann Lynch, Ping Yee Billie Au, Fernando Eduardo Ayala Valenzuela, Carolyn Brown, Diane Masser-Frye, Marilyn Jones, Leslie Patron Romero, Wenhui Laura Li, Erin Thorpe, Laura Hecher, Jessika Johannsen, Jonas Denecke, Vanda Mcniven, Anna Szuto, Emma Wakeling, Vincent Cruz, Valerie Sency, Heng Wang, Juliette Piard, Fanny Kortüm, Theresia Herget, Tatjana Bierhals, Angelo Condell, Bruria Ben-Zeev, Simranpreet Kaur, John Christodoulou, Amelie Piton, Christiane Zweier, Cornelia Kraus, Alessia Micalizzi, Marina Trivisano, Nicola Specchio, Gaetan Lesca, Rikke S Møller, Zeynep Tümer, Maria Musgaard, Benedicte Gerard, Johannes R Lemke, Yun Stone Shi, Anders S Kristensen

Faculty, Staff and Students Publications

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1–GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally.

Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function or gain-of-function properties, whereas 13 appeared neutral.

We collected detailed …

Association Of Minor Electrocardiographic (Ecg) Abnormalities With Epilepsy Duration In Children: A Manifestation Of The Epileptic Heart?, Brittnie Bartlett-Lee, Leslie Dervan, Christina Miyake, R Scott Watson, See Wai Chan, Anne E Anderson, Yi-Chen Lai

Faculty, Staff and Students Publications

Purpose: Cardiac abnormalities resulting from chronic epilepsy ("the epileptic heart") constitute a well-recognized comorbidity. However, the association of cardiac alterations with epilepsy duration remains understudied. We sought to evaluate this association using electrocardiogram (ECG).

Methods: We prospectively enrolled children between 1 months and 18 years of age without known cardiac conditions or ion channelopathies during routine clinic visits. ECGs were categorized as abnormal if there were alterations in rhythm; PR, QRS, or corrected QT interval; QRS axis or morphology; ST segment or T wave. An independent association between ECG abnormalities and epilepsy duration was evaluated using multivariable logistic regression modeling. …

Development Of A Weight-Band Dosing Approach For Vosoritide In Children With Achondroplasia Using A Population Pharmacokinetic Model, Yulan Qi, Ming Liang Chan, Diane R Mould, Kevin Larimore, Elena Fisheleva, Anu Cherukuri, Jonathan Day, Ravi Savarirayan, Melita Irving, Carlos A Bacino, Julie Hoover-Fong, Keiichi Ozono, Klaus Mohnike, William R Wilcox, Michael B Bober, Joshua Henshaw

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVE: Vosoritide is a recently approved therapy for achondroplasia, the most common form of disproportionate short stature, that has been shown to be well tolerated and effective in increasing linear growth. This study aimed to develop a population pharmacokinetic (PPK) model to characterize pharmacokinetics (PK) of vosoritide and establish a weight-band dosing regimen.

METHODS: A PPK model was developed using data from five clinical trials in children with achondroplasia (aged 0.95-15 years) who received daily per-kg doses of vosoritide. The model was used to simulate expected exposures in children with a refined weight-band dosing regimen. Simulated exposure was …

Bi-Allelic Acbd6 Variants Lead To A Neurodevelopmental Syndrome With Progressive And Complex Movement Disorders, Rauan Kaiyrzhanov, Aboulfazl Rad, Sheng-Jia Lin, Aida Bertoli-Avella, Wouter W Kallemeijn, Annie Godwin, Maha S Zaki, Kevin Huang, Tracy Lau, Cassidy Petree, Stephanie Efthymiou, Ehsan Ghayoor Karimiani, Maja Hempel, Elizabeth A Normand, Sabine Rudnik-Schöneborn, Ulrich A Schatz, Marc P Baggelaar, Muhammad Ilyas, Tipu Sultan, Javeria Raza Alvi, Manizha Ganieva, Ben Fowler, Ruxandra Aanicai, Gulsen Akay Tayfun, Abdulaziz Al Saman, Abdulrahman Alswaid, Nafise Amiri, Nilufar Asilova, Vorasuk Shotelersuk, Patra Yeetong, Matloob Azam, Meisam Babaei, Gholamreza Bahrami Monajemi, Pouria Mohammadi, Saeed Samie, Selina Husna Banu, Jorge Pinto Basto, Fanny Kortüm, Mislen Bauer, Peter Bauer, Christian Beetz, Masoud Garshasbi, Awatif Hameed Issa, Wafaa Eyaid, Hind Ahmed, Narges Hashemi, Kazem Hassanpour, Isabella Herman, Sherozjon Ibrohimov, Ban A Abdul-Majeed, Maria Imdad, Maksudjon Isrofilov, Qassem Kaiyal, Suliman Khan, Brian Kirmse, Janet Koster, Charles Marques Lourenço, Tadahiro Mitani, Oana Moldovan, David Murphy, Maryam Najafi, Davut Pehlivan, Maria Eugenia Rocha, Vincenzo Salpietro, Miriam Schmidts, Adel Shalata, Mohammad Mahroum, Jawabreh Kassem Talbeya, Robert W Taylor, Dayana Vazquez, Annalisa Vetro, Hans R Waterham, Mashaya Zaman, Tina A Schrader, Wendy K Chung, Renzo Guerrini, James R Lupski, Joseph Gleeson, Mohnish Suri, Yalda Jamshidi, Kailash P Bhatia, Barbara Vona, Michael Schrader, Mariasavina Severino, Matthew Guille, Edward W Tate, Gaurav K Varshney, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne …

Molecular Profiling Of A Hepatocellular Neoplasm Not Otherwise Specified (Hcn-Nos) Demonstrates Distinct Molecular Features In Hepatoblastoma And Hcc-Like Components, Yan Chen Wongworawat, Stephen F Sarabia, Martin Urbicain, Paola Francalanci, Pavel Sumazin, Rita Alaggio, Dolores H López-Terrada

Faculty, Staff and Students Publications

Hepatoblastomas (HB) are embryonal tumors with quiet genomes diagnosed mostly in children under 3 years of age and often cured by surgical resection and chemotherapy. However, a subset of HBs behave aggressively, displaying characteristic histologic features and higher genomic instability. Hepatocellular neoplasm-not otherwise specified (HCN-NOS) is a provisional diagnostic category for tumors exhibiting either intermediate or a combination of both HB and hepatocellular carcinoma (HCC) histological features. In this study, we characterized an HCN-NOS diagnosed in a 3-year-old patient presenting with a liver mass, in which both HB and HCC histological components were amendable to macro-dissection and molecular profiling. The …

Biallelic Med27 Variants Lead To Variable Ponto-Cerebello-Lental Degeneration With Movement Disorders, Reza Maroofian, Rauan Kaiyrzhanov, Elisa Cali, Mina Zamani, Maha S Zaki, Matteo Ferla, Domenico Tortora, Saeid Sadeghian, Saadia Maryam Saadi, Uzma Abdullah, Ehsan Ghayoor Karimiani, Stephanie Efthymiou, Gözde Yeşil, Shahryar Alavi, Aisha M Al Shamsi, Homa Tajsharghi, Mohamed S Abdel-Hamid, Nebal Waill Saadi, Fuad Al Mutairi, Lama Alabdi, Christian Beetz, Zafar Ali, Mehran Beiraghi Toosi, Sabine Rudnik-Schöneborn, Meisam Babaei, Pirjo Isohanni, Jameel Muhammad, Sheraz Khan, Maha Al Shalan, Scott E Hickey, Daphna Marom, Emil Elhanan, Manju A Kurian, Dana Marafi, Alihossein Saberi, Mohammad Hamid, Robert Spaull, Linyan Meng, Seema Lalani, Shazia Maqbool, Fatima Rahman, Jürgen Seeger, Timothy Blake Palculict, Tracy Lau, David Murphy, Niccolo Emanuele Mencacci, Katharina Steindl, Anais Begemann, Anita Rauch, Sinan Akbas, Ayça Dilruba Aslanger, Vincenzo Salpietro, Hammad Yousaf, Shay Ben-Shachar, Katarina Ejeskär, Aida I Al Aqeel, Frances A High, Amy E Armstrong-Javors, Seyed Mohammadsaleh Zahraei, Tahereh Seifi, Jawaher Zeighami, Gholamreza Shariati, Alireza Sedaghat, Samaneh Noroozi Asl, Mohmmad Shahrooei, Giovanni Zifarelli, Lydie Burglen, Claudia Ravelli, Johannes Zschocke, Ulrich A Schatz, Maryam Ghavideldarestani, Walaa A Kamel, Hilde Van Esch, Annette Hackenberg, Jenny C Taylor, Lihadh Al-Gazali, Peter Bauer, Joseph J Gleeson, Fowzan Sami Alkuraya, James R Lupski, Hamid Galehdari, Reza Azizimalamiri, Wendy K Chung, Shahid Mahmood Baig, Henry Houlden, Mariasavina Severino

Faculty, Staff and Students Publications

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± …

Germline Pathogenic Smarca4 Variants In Neuroblastoma, Leora Witkowski, Kim E Nichols, Marjolijn Jongmans, Nienke Van Engelen, Ronald R De Krijger, Jennifer Herrera-Mullar, Lieve Tytgat, Armita Bahrami, Helen Mar Fan, Aimee L Davidson, Thomas Robertson, Michael Anderson, Martin Hasselblatt, Sharon E Plon, William D Foulkes

Faculty, Staff and Students Publications

Heterozygous germline pathogenic variants (GPVs) in SMARCA4, the gene encoding the ATP-dependent chromatin remodeling protein SMARCA4 (previously known as BRG1), predispose to several rare tumour types, including small cell carcinoma of the ovary, hypercalcemic type, atypical teratoid and malignant rhabdoid tumor, and uterine sarcoma. The increase in germline testing of SMARCA4 in recent years has revealed putative GPVs affecting SMARCA4 in patients with other cancer types. Here we describe 11 patients with neuroblastoma, including four previously unreported cases, all of whom were found to harbour heterozygous germline variants in SMARCA4. Median age at diagnosis was 5 years (range 2 …

Cord Blood Transplantation For Nonmalignant Disorders: Early Functional Immunity And High Survival, Caridad Martinez, Paibel Aguayo-Hiraldo, Natalia Chaimowitz, Lisa Forbes, Nicholas Rider, Sarah Nicholas, Filiz Seeborg, Javier Chinen, Ivan Chinn, Carla Davis, Howard Roseblatt, Lenora Noroski, Bilal Omer, Tami John, Khaled Yassine, Swati Naik, John Craddock, Saleh Bhar, Carl Allen, Nabil Ahmed, Ghadir Sasa, David Steffin, Erin Doherty, Anil George, Baheyeldin Salem, Brian Friend, Meenakshi Hegde, Malcolm K Brenner, Helen E Heslop, Ann Leen, Amanda Peña, Mengfen Wu, I Celine Hanson, Robert A Krance

Faculty, Staff and Students Publications

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. Fifty-five children were enrolled, median age 5 months (range, 1-111 months); primary immune deficiency (45), metabolic (5), hemophagocytic lymphohistiocytosis (1), and hematologic disorders (4). Twenty-six patients …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, F Graeme Frost, Marie Morimoto, Prashant Sharma, Lyse Ruaud, Newell Belnap, Daniel G Calame, Yuri Uchiyama, Naomichi Matsumoto, Machteld M Oud, Elise A Ferreira, Vinodh Narayanan, Sampath Rangasamy, Matt Huentelman, Lisa T Emrick, Ikuko Sato-Shirai, Satoko Kumada, Nicole I Wolf, Peter J Steinbach, Yan Huang, Undiagnosed Diseases Network, Barbara N Pusey, Sandrine Passemard, Jonathan Levy, Séverine Drunat, Marie Vincent, Agnès Guet, Emanuele Agolini, Antonio Novelli, Maria Cristina Digilio, Jill A Rosenfeld, Jennifer L Murphy, James R Lupski, Gilbert Vezina, Ellen F Macnamara, David R Adams, Maria T Acosta, Cynthia J Tifft, William A Gahl, May Christine V Malicdan

Faculty, Staff and Students Publications

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development …

Natural History Of Tango2 Deficiency Disorder: Baseline Assessment Of 73 Patients, Christina Y Miyake, Erica J Lay, Claudia Soler-Alfonso, Kevin E Glinton, Kimberly M Houck, Mustafa Tosur, Nancy E Moran, Sara B Stephens, Fernando Scaglia, Taylor S Howard, Jeffrey J Kim, Tam Dam Pham, Santiago O Valdes, Na Li, Chaya N Murali, Lilei Zhang, Maina Kava, Deane Yim, Cheyenne Beach, Gregory Webster, Leonardo Liberman, Christopher M Janson, Prince J Kannankeril, Samantha Baxter, Moriel Singer-Berk, Jordan Wood, Samuel J Mackenzie, Michael Sacher, Lina Ghaloul-Gonzalez, Claudia Pedroza, Shaine A Morris, Saad A Ehsan, Mahshid S Azamian, Seema R Lalani

Faculty, Staff and Students Publications

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD.

METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review.

RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at …

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lise E Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E Schunk, Michael J Stoner, Arleta Rewers, Julie K Mcmanemy, Kimberly S Quayle, Jennifer L Trainor, Leah Tzimenatos, Jonathan E Bennett, Maria Y Kwok, Sage R Myers, Kathleen M Brown, T Charles Casper, Cody S Olsen, Nicole S Glaser

Faculty, Staff and Students Publications

Background: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods: We included children from 12 centers who were < 18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate < 15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results: Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children < 6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions: Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher risk of cerebral injury.

Atrial Standstill In The Pediatric Population: A Multi-Institution Collaboration, Taylor S Howard, David Y Chiang, Scott R Ceresnak, Virginie Beausejour Ladouceur, Robert D Whitehill, Richard J Czosek, Timothy K Knilans, Agnethe M Ahnfeldt, Malene Lando Borresen, Edgar Jaeggi, Sharmila Udupa, Robert Gow, Jeremy P Moore, Roberto G Galloti, Doug Y Mah, Jeffrey J Kim, Santiago O Valdes, Dianna M Milewicz, Christina Y Miyake

Faculty, Staff and Students Publications

Background: Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited.

Objectives: The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS.

Methods: This was a retrospective multicenter study of patients < 18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed.

Results: Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were …

A Toddler With New Seizures, Progressive White Matter Lesions, And Multifocal Microhemorrhages, Dana Tlais, Stephanie Fetzko, Nitya Gulati, Huy Brandon D Tran, Sarah Risen, Yi-Chen Lai

Faculty, Staff and Students Publications

A 16-month-old, previously healthy male is hospitalized for new onset seizures. Initial investigation is significant for enterovirus/rhinovirus respiratory infection, abnormal T2 signal predominantly in the white matter and scattered microhemorrhages on brain MRI, transaminitis, and thrombocytopenia. His symptoms initially improve on steroid therapy and he is discharged from the hospital. During the ensuing month with the tapering of the steroids, he develops new motor deficits for which he is rehospitalized. His laboratory investigation on readmission is unremarkable. However, there is significant progression of white matter lesions and microhemorrhages on repeat MRI. While in the hospital, he becomes febrile and has …

Temporal Changes In Gastrointestinal Fungi And The Risk Of Autoimmunity During Early Childhood: The Teddy Study, Thomas A Auchtung, Christopher J Stewart, Daniel P Smith, Eric W Triplett, Daniel Agardh, William A Hagopian, Anette G Ziegler, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Åke Lernmark, Beena Akolkar, Jeffrey P Krischer, Kendra Vehik, Jennifer M Auchtung, Nadim J Ajami, Joseph F Petrosino

Faculty, Staff and Students Publications

Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study, we examine stool samples of 888 children from 3 to 48 months and find considerable differences between fungi and bacteria. The metagenomic relative abundance of fungi was extremely low but increased while weaning from milk and formula. Overall fungal diversity remained constant over …